In this informative webinar, UCSF breast surgeon Shoko Emily Abe, MD, reviews current evidence informing breast cancer screening, diagnosis and treatment. She discusses screening guidelines and the controversies around them, genetic and lifestyle risk factors, and risk reduction strategies. Dr. Abe highlights the latest diagnostic and treatment advances, including genomic assays that enable treatment de-escalation and improved outcomes. She also outlines innovations in surgery and radiation that support personalized, minimally invasive care. The session concludes with practical insights on survivorship and the crucial role of primary care physicians and gynecologists in long-term follow-up.
Great, thank you for the introduction, Virginia. Um, thanks everyone for joining, and I'm going to go and share my slides here. OK. So, I know this is kind of a broad topic that I'm kind of broaching and um I'm, I'm jumping in for my partner, uh, who unfortunately, her schedule didn't quite work out, and um I know it was a broad topic that she was trying to put together, and so I've made some of my adjustments on these slides along the way, but we'll have plenty of time, hopefully at the end to go over any specific questions. Um, so, Just to review the objectives, I'm gonna quickly go over, not so much the details of epidemiology, but talk about risk factors. We'll talk about screening for breast cancer and some of the controversy surrounding it, which I know you're all probably very familiar with. Uh, we'll talk about diagnostics and treatment advances that we've made. Um, and then I also want to conclude with talking about survivorship and particularly the role of our primary care colleagues and how important they are in this process. Uh, so, As a lot of you may know, breast cancer is one of the most common cancers, um, especially in women, it's still the number one cancer in terms of incidence. Uh, lung cancer still surpasses it in terms of mortality, uh, but it is very common. 1 in 8 women in their lifetime will develop breast cancer, and we're talking about this 1 in 8 as in, by the time you reach about age 80 or so, um, you know, there's gonna be 1 in 8 women who have had breast cancer. Mortality is certainly decreasing and survival is improving, um, but the incidence remains high and disparities do exist in terms of treatments and treatment outcome. I think those are some of the things that we're trying to focus on, uh, going forward. And it's definitely, uh, an increasing number of survivors, survivors of not only breast cancer, but a lot of different types of cancer, and that's really reshaping how we follow them and what we do for them in the long term. Um, I want to touch upon some of the risk factors, um, and things about things to think about in terms of prevention. There are obviously the non-modifiable risk factors, things like age, which I usually tell patients age is one of the main, you know, consistent driving factors of breast cancer risk, that as you get older, especially as we go into our 70s and 80s as women, our breast cancer risk just keeps going up. Um, so obviously that's something we can modify. Uh, family history, also something we can't change, you know, a family history that is heavy in breast cancer, particularly at a young age, that might point to a genetic mutation, in fact, but any kind of family history of breast cancer certainly adds to our breast cancer risk. And then actually having a genetic mutation, whether that's the BRCA1 or 2 mutation. Uh, that the P53 mutation, the PAB2 mutations, those mutations can also increase your risk of breast cancer and obviously not something that we could change. Other modifiable risk factors or modifiable risk factors are things like alcohol consumption. Again, a big topic that, you know, is not a new topic by any means in terms of cancer risk, but again has been recently brought to light, that perhaps any amount of alcohol consumption increases cancer risk. Um, it, you know, when I, when it comes down to talking to patients one on one, I do tell them that in the end moderation is key, but certainly, if they could go without having any alcohol, you know, kudos to them. Um, I've also heard from my primary care colleagues that the idea of one glass of wine a day is actually good for your heart. Um, you know, maybe that's even a controversial statement to make these days is what I've been told. Nevertheless, alcohol consumption, you know, is something where there's probably multiple confounding factors that add to cancer risk, not the literal alcoholic effect itself. So there's still a lot that's being looked at, but definitely something that we talked to patients about, especially if they do. Um, have a history or are currently uh drinking large amounts of alcohol. Now adding to that is obesity, you know, obviously that's a big issue just across the board in terms of patients overall health. We do know that obesity does increase the risk of breast cancer, um, and a number of other cancers. Um, which also can leads to the discussion about inactivity. A sedentary lifestyle we know is not good in general, but again, we know that this adds to breast cancer risk. And in fact, for breast cancer survivors, increasing their activity level has been shown to decrease recurrence risk, so that we know that that's a big portion of breast cancer risk and future survival for patients with breast cancer. So what are things that we can do to lower risk? Chemo prevention is something that we, as specifically as breast cancer surgeons and uh medical oncologists might talk to patients about. A lot of you may have heard of tamoxifen, you know, it's been around for a long time. And tamoxifen, studied and well known as an agent to decrease recurrence risk for someone who's had breast cancer. But it has certainly been studied in a setting of someone who is considered higher risk, and can it be used to lower that breast cancer risk? And the answer is yes. And nowadays, we can actually use a lower dose uh version, if you will, called Batam, basically taking a quarter of the dose to effectively lower the uh future breast cancer risk by 50%. Uh, Roxxifene also been around for a while, another good medication, oftentimes used for postmenopausal women, to lower the risk of future breast cancer. Um, so, you know, when we counsel patients on, especially patients that we see who are considered higher risk, these modifiable risk factors and chemo prevention are things that we do talk about to help lower their risk of future breast cancer. So, the big topic of a screening guidelines, and this is, again, a hot topic, nothing new. There's been so many different iterations of the US Preventive Services Task Force recommendations, and certainly as we gain more knowledge and evidence about breast cancer and breast cancer risk, according to age, you know, we're trying to better kind of personalize our screening approach, but still, when it's, you know, guideline based, we have to kind of give these generalized recommendations. And granted, the screening guidelines are for women who are considered average risk, so, not with a significant family history or genetic mutation or a previous biopsy that showed atypical lesions. So, average risk women, again, the US Preventive Services Task Force most recently said biennial, or, you know, every other year mammograms start at age 40, um, versus Um, uh, the Cancer Society, American Cancer Study said, start annually at 45, but then after, once you reach 55, then go biennial. And this is the idea based on the fact that women, postmenopausally will tend to develop very slow growing cancers, and therefore going biennial will probably be fine, meaning that in a two-year span, a tiny cancer that may have developed in the interim is probably not going to grow substantially. Now that does potentially Cause you to miss the aggressive breast cancer. But those, you might even miss, even if, I wouldn't say miss, but those are called interval cancers, and patients will develop sometimes a rapidly growing cancer within 4 months of having a normal mammogram. But I'd like to say, this is again for average risk women. I do want to point out the biannual recommendation often gets misconstrued by the lay person typically, that it means you're you're not likely to get cancer after 55. And I have to remind patients that that's not quite true. Your risk does go up, but it's just that the cancer you develop is likely going to be a slow growing kind, where a biennial mammogram will pick it up just fine when it's still small. Uh, the NCCN guidelines, kind of the, the Bible, if you will, of the cancer field, the National Comprehensive Cancer Network guidelines still states start at age 40. Now that is different from women who are considered high risk, as I mentioned, women who have genetic mutations, who have a significant family history of breast cancer or who have had previous biopsies showing what we call atypical ductal hyperplasia, or even lobular carcinoma in situ or LCIS. Those are considered high risk lesions, not necessarily obligate precursor to cancer, but definitely a lesion that tells us they're at high risk of getting breast cancer in the future. And so for those high risk women, we recommend mammograms yearly, and then we add breast MRI on top, um, yearly also as well, and we tend to stagger them by every 6 months, so that they're getting watched much more closely than just once a year mammogram. We add the MRI once a year, and then by staggering it every 6 months, they're getting some kind of breast imaging. Now, this, this screening uh topic in and of itself could be a whole hour, I guess, discussion, but all to say, again, we're trying to become better at personalizing screening regimens, because there are obviously women who are average risk or per possibly very low risk for future breast cancer. And so can those women really, you know, forego the yearly mammogram that's being recommended, which, by the way, in other countries in this world, annual mammograms are not happening. It's biennial sometimes every 3 years at most. So we are definitely on the side of screening a lot more um and holding onto that yearly mammogram, but there is also plenty of data that shows that. You know, particularly for younger women who have a little higher propensity of developing those aggressive type of breast cancers, without the annual mammogram, we are going to miss a good portion of these aggressive breast cancers potentially. So we are lucky that in this country at this point, we are allowed the luxury of typically ordering annual mammograms and having it approved and covered by insurance. So that's where again the personalized screening process um comes in, and we have a trial that's not unique to UCSF but we do spearhead. It's called the WIsdom trial, which a lot of you may have already heard about this or are familiar with this, but it's a great study to really try to see how can we better personalize breast cancer screening. And I put on here, woodshastudy.org is a website where you can learn more about it, but I'll talk about it a little bit here. Um, so, it's a trial that allows women of age 30 to 74, um, to find out what is the best way for them to be screened for breast cancer. Um, and again, they could be anywhere in the United States. They don't have to be at UCSF or get their mammograms done here. What they're going to basically be asked to do is get their breast cancer screening done, whatever the recommendation may be annual mammograms, biennial, whatever it might be and send the report into the Wisdom trial and as well as answer surveys so that we can monitor them to see how they're doing. Has there been any development of breast cancer. Um, and it's comparing two screening approaches. One is the annual mammogram starting at age 40, and I will say that any woman who is under age 30 is gonna go into this personalized screening plan, again, because under the age of 40, usually they're not going to get approval to get a mammogram yearly. But when the patients can choose which group they go into ultimately, so it's not exactly a randomized trial per se. There is basically, um, they do allow for patients to select. But the key thing here is we do a full risk assessment. And what that entails is for a lot of women, um, not only just questionnaire regarding their overall health, family history, etc. but they can get a genetic testing kit done by color. And they're looking at those um typical, you know, genetic mutations that we talk about when, when we talk about breast cancer risk, but they will also look at what we call nucleic polymorphisms, very specific alterations in the genetic code, that may be adding to their breast cancer risk. Uh, so it's a very unique way of actually doing a risk assessment, so it's not your typical Gale model or Tarausic model, which you may have all heard of. Um, and then based on those results, the breast health specialists will be in contact with them to recommend a screening regimen. And it's no cost to participate, and again, can be done by any woman anywhere in the in in the country really. And there's very really little that any primary care doctor or OBGYN that's um ordering or ordering the mammograms for these patients, there's nothing really that you have to do. And in fact, you could just direct them to the wisdomstudy.org for them to look at the study and enroll in it. And there's again, very little downside. And in fact, again, the hope is to better personalized, uh, personalized breast cancer screening. Technique wise, um, I'll talk about the innovations in mammography. A lot of you may have already seen plenty of mammogram reports saying there are 3D or tomosynthesis magmograms. You know, it's at this point has been around well over 10 years, and I would say that at most breast centers, it's become the standard of care. Um, it allows basically, initially, the a lot of the data pointed to that less callback was the biggest benefit, meaning they could scan through the breast tissue and tell if maybe just normal, um, uh, overlap of normal dense breast tissue, um, was what looked like a mass or not. So less callback rate was the biggest big significant impact initially. But further studies have shown that, yes, it is more sensitive in picking up breast cancer early, so there's definitely a big benefit. I think a lot of patients have and still continue to question, is there more radiation involved with the tomosynthesis. And I generally tell patients that no, it is not a significantly larger amount, and in fact, the 3D uh mammogram, the scan that they do. They don't have to repeat a 2D mammogram on top of it, which was sometimes the way that it was done previously. Nowadays, the 2D image is created from the 3D scan that they do. So again, it goes back to the safety of this is of it, and in fact that it increases the chance of potentially having come come back for more mammograms, right? So, In the end, I feel like there's just definitely a bigger benefit to it. Certainly with more sensitive studies, there's always a question of, are we losing the specificity and are we still picking up other random things. But again, the increase in specificity in basically ruling out the false positives has been a significant impact. Um, contrast enhanced mammography is another thing that's uh relatively new. And this is still in a mammogram machine, but a patient gets the iodine, iodinated uh based contrast, like a CT scan, and so it's looking at what we call the functional status of the breast. So it's looking at blood flow into the breast tissue. And so this is very similar to an MRI in that sense, because the beauty of the MRI scan is that contrast is given so that we could look at the, the blood flow into the breast tissue. And the idea is that things that are cancerous, obviously want a lot of blood flow, and so we were we're going to see this enhancement in these specific areas. So, contrast enhanced mammography against using the same kind of concept of a vascular supply to which part of the breast, how is it enhancing, and if it is, can we target that to do a biopsy? Um, now, contrast enhanced mammography, the difficult thing right now is that for most institutions and most insurances, it's considered a diagnostic study, and that's where the hiccup is right now and trying to order it as a screening um study for a lot of women. Um, and that might be changing hopefully as we get more data, and as we get approval to use this as a screening tool. But it is a very, very useful tool, especially in places that breast MRIs are not readily available, or women have um perhaps very dense breast tissue, where even with a 3D mammogram, there's a lot of questionable findings. Contrast enhanced mammography could be a very helpful next step. Um, as I mentioned, MRI used for high risk women, that has been around for quite some time, and again, it's a functional study, which is what separates it from just a two dimensional image that like a mammogram or ultrasound is even. And so it has the ability to detect things that a mammogram or ultrasound might miss. Again, areas of high vascular activity, what we call enhancement. But the downside of an MRI is that because it is so sensitive, it does pick up a lot of benign things or would end up being benign. So it does have a high false positive rate. And that's where I think the counseling about using breast MRIs is important before we do it, and certainly at this point, it is reserved for generally women who are considered high risk. So genetic mutation carriers, women who calculate at high risk based on family history, or who have a history of a biopsy showing atypia or lobular carcinoma in situ. And certainly we do use MRI as follow-up for women who have had a history of breast cancer. Um, but again, not every woman requires MRI follow-up, um, for a lot of my patients who had very early stage cancer, um, without dense breast tissue on mammogram, we could follow them with mammograms yearly. Um, another controversial topic and a lot of questions I get from patients, um, and colleagues alike is ultrasound screening. Um, to put it simply, I think it's still kind of controversial. I don't think it's quite ready for general use. Um, I think it holds a lot of promise because obviously it's not using radiation. It's generally speaking, a much more comfortable test to undergo. Um, ultrasounds generally, traditionally have, you know, not been used as a screening tool for breast cancer screening because number one, There is a lot of operator dependence, meaning which ultrasound machine are you using, in what setting, and who's doing the study can make a big difference. It could pick up a lot of artifacts, so there is this concern of a lot of false positive. On the other hand, it's not very sensitive to pick up very early signs of cancer, like calcifications on a mammogram. It is not going to pick those things up. So, In that sense, that's why it's not a great screening tool. Now, there's been automated ultrasound, breast ultrasounds, um, Abus that has been looked at. I feel like that hasn't been widely utilized or accepted, even though it took the operator dependence out of it somewhat, because again, the ultrasound itself is not quite sensitive to, again, pick up some early signs of breast cancer, and it could still have some artifact. I could speak from just experience of seeing a lot of patients come to me after their You know, AIS or a screening ultrasound of some type, or even these QT scans that are being done, is that they find a finding, and then what they tell you is to go get a mammogram and ultrasound to, to see what it is or see if we could find it and then biopsy it appropriately. And so it does again lead to this essentially a false positive, because oftentimes they'll go through the rest of the treatment course or a diagnostic course, and we don't find anything. And now the patient is left with this question of like, is it really nothing or are we just not seeing it, uh, you know, and it adds that level of anxiety, ultimately. So again, ultrasound not quite ready, I think, to be used as a generalized screening tool for breast cancer, but I think there's, you know, a lot of good promise and still research that is ongoing. Um, so going into the genetics, which I kind of keep mentioning about genetic testing, um, and this is something that, you know, you may encounter in your patients who are coming in for their, you know, regular annual visits, um, and as you're going through their history, you know, you do notice that they do have, um, a family history of certain cancer patterns. And, you know, sometimes it's hard to discern if a certain cancer pattern really is indicative of a genetic mutation or not. Um, and with the constant, you know, knowledge that we're gaining from the genetics world, you know, certainly, you know, referring to a cancer center, referring to a geneticist who could then talk to the patient and really tease out if their genetic, you know, or family history is indicative of something or that they should get genetic testing. I think that's the first step. But certainly, Kind of knowing about their family history, if there's any cancer pattern that you think is a little bit unusual, concerning, I think it's, you know, fair game to to send them to a geneticist. And again, these days with, you know, telehealth visits, at least right now being allowed, it's um an easy thing that you could refer to us, and our geneticists could always go over their family history and really delve into um the full family tree to see if genetic testing is warranted or not, and really go into also. The risks and benefits, if you will, and the pros and cons, um, and the ramifications of doing genetic testing. Um, you know, with all of this risk-based screening that we're doing, genetic testing, again, our hope is to better tailor screening for patients and, and really do what is gonna maximally benefit them, and obviously minimize the risk of unnecessary testing, um, etc. So, From there, I wanted to go into actually talking about breast cancer and breast cancer treatment. Um, and it's gonna be kind of a general broad overview because I'm gonna touch upon surgical things, things that um are related to what medical oncologists will do, and granted, I'm not a medical oncologist, but that part is quite fascinating because that is where a lot of the um great advancements in breast cancer treatment has come from. And we'll talk about again, how we better tailor treatments um for breast cancer patients. Um, Let me go back actually. Um, on the slide, you know, you may have heard of tumor receptor types in breast cancer, and, you know, for a long time we've always looked at the estrogen receptor, progesterone receptor, and HER2 receptor as the three standard receptors that we look at to really classify what kind of breast cancer is this, and then to really decide on what kind of targeted therapy are going to be appropriate. If it's estrogen receptor, progesterone receptor positive, which we call hormone receptor positive, taking some kind of hormone blocker like tamoxifen, as I mentioned earlier, or an aromatase inhibitor is going to be appropriate. If it's HER2 positive, then giving HER2 targeted medications along with chemotherapy is going to be appropriate. But if it's all 3 are negative, which we call triple negative breast cancers, and you may have heard this as being the most aggressive type, then there's going to be a different combination of chemotherapy agents that we would give, along with the immunotherapy. So there's just a variety of treatment options depending on their receptor results. And what's really interesting is, not only are those receptor results really crucial, but it's these genomic assays that really help us really decide what kind of treatment is going to be appropriate because not every breast cancer patient needs chemotherapy, number one, which is potentially the most, I would say, Devastating for a lot of patients, meaning just going through treatment is not easy by any means, even in the lightest version of chemotherapy, if you will, that we give, it is still not easy for anyone to go through chemotherapy, and it could have potentially long-term side effects. So we really want to be smart and really tailor treatments according to the patient and their breast cancer type. And these genomic assays, um, Oncotype DX is one of them that's been around for a long time in MammaPrint. Those two are assays that we run on invasive carcinoma to determine if chemotherapy would be of benefit. Um, Oncotype DX MammaPrint, both are equally good, um, looking at different, what we call molecular markers or tumor DNA markers to basically give us a score in a report that says, yes, this cancer is high risk and you will benefit from chemotherapy, meaning it will improve your survival. And so that's what really drives our decision about chemotherapy these days. Or will it tell us that it's low risk and therefore, you're not really gonna benefit from chemotherapy. So that in combination with the actual stage of the cancer, in stage meaning the tumor size, the lymph node status, meaning is, are there any positive lymph nodes? That's what's gonna help guide the medical oncologist in deciding what the patient is chemotherapy gonna be of benefit for you? And in doing so, we've been able to safely de-escalate patients for a lot of patients that we traditionally may have said, you need chemotherapy. For instance, the young patient, perhaps maybe 50 years old, who has a relatively small breast cancer, but one lymph node positive. Well, before these genomic assays, we would have said you should do chemotherapy. You're young and there's one positive lymph node, so let's just go ahead and do it. But nowadays, we would run Oncotype DX MammaPrint to really understand the biological nature of the cancer to determine is chemotherapy going to benefit you. And there's certainly a fair number of women who we find that biologically their cancer is not going to be sensitive to chemo, it is not going to improve their survival. And what I mean by improving survival is lowering the risk of recurrence and specifically lowering the risk of a metastatic recurrence, because that's what, you know, affects someone's survival and mortality. So, Lymph node positive doesn't mean you automatically need um chemo, and in fact, those types of cancer are more sensitive to the hormone blocker. So going on the hormone blocker pills, that's gonna be more crucial to them. Uh, decision RT mentioned here under genomic assays, that's used for DCIS, that's the pre-cancerous, if you will, or pre-invasive, um, cancer. And, you know, DCIS. We've traditionally treated as breast cancer for decades, um, and it had to do with the fact that we were concerned about its progression eventually into cancer. So we tended to do the surgery, remove it, get a clear margin, follow it with radiation for potentially 5 weeks, and then take your hormone blocker, if it's estrogen receptor positive, for 5 years. Treat it like breast cancer, basically. Nowadays, we know that that is probably a little bit overkill for a lot of women with very small DCIS or non-aggressive type of DCIS. So this decision RT study was uh test was designed to determine in which patients with DCIS, you know, who needs radiation after their lumpectomy versus who doesn't really benefit much from it. So, again, another way of tailoring um their treatment to their DCIS or cancer type. Um, just to touch upon that point for a lot of women with early stage breast cancer, They don't necessarily, definitely don't need mastectomy necessarily, unless they have a genetic mutation, their improvement, their survival is no different between lumpectomy and mastectomy. You know, that's something we've known for decades. But certainly some women with early stage breast cancer, they could get a lumpectomy, and if it's truly early stage non-aggressive type, they could safely forego radiation in a lot of cases. So that's a big thing. And I'll talk about a little bit more in in in a slide coming up, um, and perhaps just take a hormone blocker for 5 years. So, you know, this is where again, personalized approach and learning where where we can safely de-escalate therapy has been the big advancement in breast cancer treatment. So specifically in surgery, again, my area of expertise, you know, there has been some advancements. I feel like it's not nearly as rapidly advancing as the medications, um, you know, chemotherapy, immunotherapy, targeted therapy that we see now. But certainly we've gotten better at de-escalating therapy, as I just mentioned, and everyone does not need a mastectomy. We can do a lumpectomy or partial mastectomy for most women. With early stage cancer, and we could combine it with great plastic surgery techniques, and oftentimes we will work with our plastic surgery colleagues to give him the best oncologic outcome, but also great cosmetic outcomes. And something you might see patients undergoing more and more is perhaps even for a a fairly large breast cancer, we could do a large lumpectomy and combine it with a breast reduction or a breast lift. And that kind of gives patients the benefit of two things if they were already someone who considered a breast reduction in the past, is that not only are we getting to remove the cancer and get it out safely by doing a large lumpectomy, but by combining it with a breast reduction, the plastic surgeon can make that breast where I remove the cancer look very nice and match the other breast to make it even. And so this has been, you know, a great outcome, and it's probably one of the more satisfying surgeries that I do for patients. I mean, I can't take all the credit because the plastic surgeon does the, the nice uh reconstruction and the breast reduction at the same time, but that's something that we do very frequently at our institution. I think at a lot of uh um breast cancer centers, they are doing that. Um, we also do what's called total skin sparing mastectomy, or you might be hear it called nipple sparing mastectomy, and that is oncologically safe, as long as the cancer is not involving the nipple. Um, and, you know, patients do have to be of a certain size and shape of breasts to be able to do it safely, because certainly someone who is very large breasted or has a lot of ptosis, uh, we typically wouldn't, uh, offer a total skin spray mastectomy because they would be at high risk of skin necrosis and nipple necrosis. But that's where sometimes doing the first surgery with a lumpectomy and breast reduction and reducing the breast size, then allows them to be a total skin sparing mastectomy candidate by having reduced their breast size and lifted their nipple position. So there's a lot of creative ways that we're able to do these surgeries. Um, the other big change has certainly been axillary surgery, so the removal of the lymph nodes. So, I guess I don't know who's on the call, but maybe a lot of you remember the days when women had all the lymph nodes under their arm removed called an axillary dissection, which led to that high risk of lymphedema and mobility issues and chronic pain. Now, it's very rare in this day and age that we have to do axillary dissections, even for women with initially lymph node positive disease, and that's thanks to the great advancement in the systemic and medications that we have to downstage it and shrink these cancers. But most women with invasive cancer these days undergo sentinel lymph node biopsy. So that's where we're just removing just the sentinel nodes, so the first draining nodes, um, that the theoretically would be the lymph nodes under the armpit, you know, catching any cancer, trying to escape or, or, um, spread. So we find those by injecting special dyes during the surgery that track up to those lymph nodes that allow us to selectively identify those sentinel nodes, which on average is only about 2 to 3 lymph nodes. It's not a whole lot. Um, and send that to the pathologist so that they could ultimately tell us, are there any signs of cancer in the lymph nodes? And it's really at this day and age when we're discovering breast cancer early, it's a real question of, are there any cancer cells in the lymph node because imaging is looking normal and the exam is normal. And so sentinel node biopsy has been the standard of care for breast cancer patients now for, you know, well over 2 decades, but now we've come to the point where we could safely omit sentinel node biopsy and, again, a lot of early stage breast cancer patients. Patients who have um Pardon mean cancers that are less than 2 centimeters are in their menopausal ears, who don't have the aggressive subtype of breast cancer. So we're typically talking about estrogen receptor positive, progesterone receptor positive, HER2 negative breast cancers. In those patients, we have found that the sentinel node biopsy essentially isn't adding much, um, meaning it's not like we're worried about cancer in the lymph nodes, that is not the worry and why we do the lymph node surgery to begin with. It was to gain information about the lymph node status that helps guide the treatments that they would receive afterwards. Again, ideas about if your lymph nodes positive, do we need to consider chemotherapy? And as I mentioned earlier, the lymph node status is not even the main driving point of deciding on chemotherapy or not. So again, it, it highlights the fact that the lymph node part of the surgery is becoming less and less important. Um, on top of the fact that, again, early stage breast cancer patients, it's very unlikely for the cancer has spread to the lymph nodes. And so, and, and going back to even further studies done really going back to the 60s and 70s, even when we knew there were some patients with positive lymph nodes on a microscopic level, those patients do not automatically go on to develop lymph node, you know, cancer within the lymph nodes in the future, nor metastatic disease. And that speaks to the importance of, again, all the treatments that follow, namely the medications. Um So, again, this speaks to our moving forward and de-escalating therapy for a lot of our patients and avoiding a relatively small but still potentially unnecessary part of their surgery, the sentinel lymph node biopsy or any kind of lymph node surgery. So that's where we're at in terms of surgery and advancements we've made. Uh, radiation therapy, I touched upon it a little bit earlier, but again, an area where we are learning more and more of how we could de-escalate therapy. So, traditional course of radiation after a lumpectomy was typically about a 6 to 6.5 week course, um, every day, Monday through Friday. And you can imagine that a patient who is not close to cancer center or radiation therapy center, which you may have, you know, had patients like that, it's a struggle to find out where they're gonna go, how are they gonna be housed while they go through radiation. And a lot of these studies that looked at Potentially omitting radiation or doing shorter courses was done um in a place like Canada, where there are very limited amount of radiation centers, and definitely getting to those centers is difficult or um places in Europe. And what they found was basically, number one, radiation could be given safely in much shorter courses, so a little bit slightly higher doses at each session, but over a short course, and the effectiveness is just as good in terms of lowering recurrence risk, and the side effects, etc. were no different. So that's called hyperfractionation, shorter course of therapy, and we're down to about a 3 to 4 week course these days for a lot of women with breast cancer who undergo lumpectomy. Sometimes we'll do even, I say we, but the radiation oncologist will do ultra hyperfractionate courses, which is like a one-week course, and some women will qualify for that, and that's even shorter, which is great. Um, there's also partial breast radiation that could also be given the over the course of a week where they're just radiating the lumpectomy site, cause if a recurrence were to happen, that is the site of recurrence. Uh, versus the traditional course of whole breast radiation, whether it's over 1 week or over the course of 4 weeks, is given to the whole breast to decrease the recurrence risk. Now, again, uh speaking of de-escalation, we are at the point where some women could completely omit radiation therapy after the lumpectomy if they meet criteria. Criteria meaning their cancer is, again, a smaller size, but even up to 3 centimeters. So up to 3 centimeters, again, hormone receptor positive, HER2 negative. Not an aggressive subtype. Um, technically, some of these studies that looked at this, you know, they, it was in the era of having lymph node information and so that's a little bit of a controversial topic in the oncology world, but, you know, presuming the lymph nodes are negative or they had the sentinel node biopsy and it confirmed that the lymph nodes are negative, these women can safely avoid radiation. What that means is that their overall survival is not going to be any different. Um, and it goes back to the point that the breast cancer growing in the breast is not what really dictates the mortality from breast cancer ultimately. It really is making sure that they do not have metastasis or a metastatic recurrence in the future. And what's gonna help with that is, again, the appropriate medications. So, again, local therapy in terms of radiation, it doesn't affect their survival. Now, there is a slight difference in their local recurrence risk, the risk of the cancer coming back in their breast, and that recurrence risk is a difference of about 50%. So radiation will still lower the risk of uh lower the risk of recurrence, local recurrence by 50%. But that difference could mean a 4% recurrence risk if you don't get radiation versus 2% if you do. And that's what we mean by a very small difference. And if you follow those patients out 10 to 15 years, yes, the recurrence risk might start separating a bit, meaning the patient who didn't get radiation, it might go up to 8%, maybe 10% risk, while the person who did get radiation, it stays at about 5% risk. And so some patients will still choose to get the radiation for that small but definite difference. But again, in terms of survival, there's no difference, because if you think about the patients who didn't get radiation or did get radiation, They're going to be followed closely with mammograms, potentially MRIs on top of that. And if a recurrence were to happen, the idea is we're going to catch it early, and again, be able to deal with it relatively, you know, expediently, get the cancer out, get it out with clear margins, and at that point, if they choose to go under radiation, they still have that option open to them because they have not had radiation previously. So, all of these things that we're constantly doing to de-escalate therapy is really to still improve or keep the same excellent survival that most breast cancer patients have, but minimize the potential risks that come from any treatment or any type of therapy that we would suggest to them. So, as I mentioned, the systemic therapy advancements are really what's been significant, um, even within the last 5 years, and you probably hear a lot of news about the different therapies that are out there now, and it's become increasingly more confusing, even though I'm in this specialty as a surgeon, it is a lot to keep up with, and kudos to our medical oncology colleagues that are constantly doing this research and staying up with what is the newer and better therapies that are out there that are going to help their patients. And particularly when, you know, they have metastatic breast cancer patients where they're looking at 2nd, 3rd, 4th line therapies, clinical trials. So there's a lot going on constantly. As I mentioned, targeted therapy has been a big game changer. Um, I mentioned here a couple of them, CDK46 inhibitors, PARP inhibitors, and I won't go into the mechanism of action, although it is quite fascinating because we are looking at different points in um the cancer cells, um, growth activity, if you will, and finding steps where we can intervene and stop its growth. For instance, CD CDK46 inhibitors are what we call checkpoint inhibitors, um, where checkpoints are areas that cancer cells have learned to evade. Um, so anyway, so we are finding ways to manage or um utilize that step to inhibit cancer cells from growing. Um, same thing with PARP inhibitors, PARP inhibitors work well, um, are used in breast uh BRCA1 or BRCA2 mutation carriers. And so these things are used in addition to the targeted hormone blocker therapy that I mentioned earlier. Um, HER2 positive breast cancers have the great option of using many different types of HER2 directed the therapy. Um, trastuzumab was one of the earliest one. Um, now we have a multitude of HR HER2 targeted therapies and some like this trastuzumabdoxaican, which is an antibody conjugate type of drug. So it's amazing that we are utilizing kind of our immune system, if you will, to better target breast cancer, um, cells, to better transmit these drugs into the breast cancer cell also. So, um, amazing things that are being done in these, uh, targeted therapies, antibody conjugates. Um, and immunotherapy is also a big space, again, where we are harnessing our immune system or the, the patient's immune system to attack, um, the cancer cell. Pembrolizumab has been a big, big game changer in triple negative breast cancer patients. It's been around a bit longer in the uh lung cancer space and have shown great um results in there. But triple negative breast cancer patients who have one of the most aggressive types have definitely seen benefit from these um immunotherapy drugs. Now, the interesting thing is, now with immunotherapy, Um, targeted therapies, there are different sets of side effects that we need to worry about with immunotherapy, you know, the immune system being revved up, revved up, if you will, could attack other organs. So we have to worry about things about Pneumonitis, hepatitis, um, thyroiditis, all the other itises. So those are things that now that medical oncologists have to monitor for, and there can be sometimes long-term effects, um, uh, on those organs. So it's not all just, oh yeah, we get to avoid chemotherapy because these drugs are oftentimes given with chemotherapy, and now there are different sets of side effects that we have to monitor for, but nevertheless, it has definitely improved the survival in these patients that didn't have much good options otherwise. So, um, another thing I wanted to touch upon, multidisciplinary care, I hope I'm OK with time. Um, Um, as you know, breast cancer care, and a lot of cancer care is gonna be multi multi-disciplinary, um, at this point, and it's a very closely kind of orchestrated, um, you know, coordination between the surgeon, medical oncologist, and the radiation oncologist, and involving the pathologist, radiologist, um, and all of our support staff. So it's really a team effort when it comes to taking care of patients. Um, and then here is where, you know, our primary care colleagues are, are so important, crucial because through their course of cancer care and the postoperative or post-care period, you know, it's still important to manage their comorbidities, obviously making sure that they're adhering to all their other medical cares and surveillance for other things because Obviously, when the cancer diagnosis comes in, that becomes a lot of times our big focus. Um, but we always try to make sure that we include our primary care colleagues, um, even if it's just to update them on what, what's going on with the patient, but, um, and, and making sure that patients are again adhering to their overall healthcare management. Um, and as I mentioned earlier, you know, this, this population of survivors is increasing more and more as patients are living longer, as patients are surviving their breast cancer and doing well. So with this growing survivor population, we have to be aware of and manage the late effects of treatment. Um, lymphedema, which is not as common as before, but we still have many women having had their surgery even just 20 years ago, where axillary dissection was still relatively common. Living with the effects of that surgery, the lymphedema risk, the chronic chronic pain and mobility, do they still need um physical therapy follow up for that, etc. Um, bone loss, you know, osteoporosis, osteopenia is also a risk with particularly hormone positive breast cancer patients who are taking the hormone blockers long term. Uh, cardiac toxicity and other toxicities from chemotherapy, and how to manage that long term. So it becomes a real kind of team again, team effort in managing these things. And, you know, I would say that a lot of patients, after about 5 years, they tend to, quote, graduate. Um, and do not have to see necessarily their oncologist or even their surgeon long term after that. But we tend to do, and I think a lot of cancers tend to do, is to have a survivorship program where patients are still monitored at least yearly in the survivorship clinics so that we can monitor these for these long-term effects. And again, make sure they're doing well and thriving. Um, and I think that is becoming more and more an important thing as patients again survive, um, longer. Some of the other um issues that we try to address during this survivorship period is, you know, addressing this fear of recurrence. You know, what are we doing to continue to monitor them? What are the appropriate screening tools that we need to use during this period. Um, talking about particularly breast cancer patients, sexual health, um, menopausal symptoms that come with taking hormone blockers, um, body image from their surgeries that they have had. What are other surgeries that can be offered to them? You know, as breast cancer survivors to help with their body image. Um, and obviously, these are things that are pretty resource heavy, and that's why we're happy to offer our survivorship and to help patients in this period still, you know, meet with the appropriate doctors or providers that could help them in this journey. And so that's where, you know, we certainly, again, you know, um, work closely and rely heavily with our primary care colleagues as much as we can, you know, everyone's busy, um, but routine health maintenance is obviously again, important in in continuing their overall health, vaccination, preventative care, chronic disease management, as you already take on, which is already a lot. Monitoring for recurrence or new cancers, what is the appropriate screening. You know, we realized there's already a lot on your plate to manage with each individual. And so what we want to try to do is to incorporate that and to add our piece in terms of what are the resources that we have, what are the things that would be appropriate for us to continue to take on in terms of managing and screening for. Um, future directions, um, as I kind of already mentioned, you know, really precision medicine, if you will, and personalizing care is really where medicine is heading in general and particularly obviously in cancer. Um, there are things called liquid biopsies that you may hear of to look for recurrences. Right now, a lot of these are being more so studied or utilized in uh monitoring patients who've had metastatic breast cancer or very advanced stage breast cancer, and looking for signs of metastatic recurrence and helping guide therapy from there, not so much used in early stage breast cancers at this point. Um, we have more and more and molecular markers that we're looking at to kind of again, better tailor treatment potentially. Um, one of the tests we have here at UCSF is called UCSF 500. And this is a more comprehensive molecular diagnostic test that looks at tumor DNA to, to identify if there are any genetic mutations that perhaps we could better target uh with certain treatments. So again, we're trying to more personalize treatment to the patient and their cancer. Um, as you know, AI seems to be taking over, well, I hope not, but there's definitely room to obviously utilize, um, you know, technology, so using AI for, um, imaging interpretation has is not anything new. I think they have utilized more computer aided, um, detection systems for a long time, and AI I think is just a newer item. of how we utilize technology to more accurately and better identify breast cancer at an early stage. Um, obviously, there's a lot of different apps, wearables, things like that to help monitor patients and using telehealth to reach out to more people, help people who are, uh, patients in rural or underserved areas, and that's been a big game changer for us as well, even if it's providing second opinions. Um, so, yeah, a lot to, a lot more to come, a lot evolving, and, you know, we continue to as an institution, look at racial and socioeconomic disparities. How do we better, um, you know, get patients, um, in for screening cause that is the first step step, making sure that Um, they are coming in, making it more accessible, etc. um, and that's where, you know, um, we again like to work with our primary care colleagues to make sure we get the word out and see where they are, um, you know, hitting issues in scheduling or getting patients in. Um, and that is, I think, the end of my talk. Oh, it's just kind of a summary of what I just said, um, Yeah, I guess encourage screening risk assessment, refer to genetics, um, and survivorship and holistic care. That's a great summary slide that Doctor Goodwin put together there.
